Sertoli Cell Proliferations of the Infantile Testis

Abstract

We report on six boys with intratubular Sertoli cell proliferations (ISCPs), studied by routine histologic methods, electron microscopy, and immunohistochemistry of anti-müllerian hormone (AMH), inhibin alpha-subunit, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), proliferative cellular nuclear antigen, and p53, and carefully followed for extended periods with periodic clinical examinations, testicular ultrasonographies, and determinations of serum levels of AMH and inhibin B. Peutz-Jeghers syndrome was found in four of six patients, and gynecomastia occurred in five of six patients. One boy had isosexual pseudoprecocity. ISCPs were observed as multiple foci of seminiferous tubules with large and proliferated Sertoli cells replacing germ cells and limited by the basement membrane. Mitotic figures, atypia, and/or interstitial invasion were not observed. Bilateral ISCPs were the only pathologic finding in three patients (patient nos. 1-3) and were associated with a microscopic tumor that resembled a large-cell calcifying Sertoli cell tumor (LCCSCT) in a fourth patient (patient no. 4). In the two remaining patients (patient nos. 5 and 6) ISCPs and LCCSCT were found in both testes. Ultrastructural examination showed large Sertoli cells, with round nuclei, sparse organelles, and some glycogen. Inhibin alpha-subunit immunolocalization was positive in the five patients in whom it was determined (patient nos. 2-6), AMH was positive in those ISCPs associated with tumors (patient nos. 4-6) and negative in isolated ISCPs (patient nos. 2 and 3); 3beta-HSD and PCNA were variable, and p53 was negative in all ISCPs. Patient nos. 1-4 have been followed for 2-19 years. One of them is currently entering puberty, the other two have already completed puberty and have testes of normal size, and the remaining one is an adult with clinically normal testes and sperm production. None of these patients had evidence of tumor development during follow-up as shown by serial ultrasonographies and serum levels of AMH and inhibin B. Patient nos. 5 and 6 who had bilateral ISCPs and LCCSCT were orchidectomized and evolved for 2-10 years after surgery without tumor recurrence. The prognostic significance of ISCPs, particularly when they are the only pathologic finding in a testicular biopsy, is a matter of controversy. Based on the long normal evolution, we recommend a conservative approach to therapy. The bilateral and multicentric character of ISCPs and their association with Sertoli tumors and Peutz-Jeghers syndrome suggest that they represent either proliferative lesions with tumorigenic potential or the intraepithelial stage in the evolution of some testicular Sertoli cell tumors.

Anti-Müllerian hormone as a marker of steroid and gonadotropin action in the testis of children and adolescents with disorders of the gonadal axis

“…AMH expression has been shown in overt Sertoli cell tumors [73, 74], in large cell calcifying Sertoli cell tumors frequently associated with Peutz-Jeghers syndrome [74], in primary or metastatic granulosa cell tumors of the testis [73], and in intratubular Sertoli cell proliferations, which has been suggested to represent an “in situ” or early stage of Sertoli cell tumors [74]. Although a single determination of serum AMH may not be helpful to establish the initial diagnosis of the tumors in most of pediatric cases, because high AMH is normally found in the prepubertal boy, increasing AMH levels may be suggestive of a progressive lesion.…”

Compensatory function of the remaining testis is dissociated in boys and adolescents with monorchidism

“…Therefore, serum AMH is a widely accepted biomarker of testicular activity during childhood (30,31,32,33,34,35,36). Furthermore, serum AMH has been postulated as a surrogate marker for the mass of functional Sertoli cells in patients with gonadal dysgenesis (37), hypogonadotropic hypogonadism (14,38) and Sertoli cell hyperplasia (39,40). In the present work, the significant correlation between testicular volume and AMH suggested that AMH levels reflect the degree of compensatory hypertrophy in prepubertal patients with monorchidism.…”

Sertoli Cell Tumor Causing Prepubertal Gynecomastia in a Boy with Peutz-Jeghers Syndrome: The Outcome of 1-Year Treatment with the Aromatase Inhibitor Testolactone

“…Although SCTAT has frequently been reported in association with PJS, only 16 male patients with PJS and Sertoli cell tumor have been described to date [4,5,6,7,8,9,10,11,12,13,14,15]. Thus, our patient is the 17th case presenting with prepubertal gynecomastia and gonadal tumor.…”